Pregnancy-Related Hypertension

Etiology and PathogenesisTop

During pregnancy the maternal cardiovascular system undergoes several major physiologic changes. As early as 8 weeks’ gestation, peripheral vasodilatation can lead to a fall in systemic vascular resistance. To mitigate this effect, maternal cardiac output steadily increases, reaching upwards of 50% above the prepregnancy levels by weeks 20 to 24. As there is usually a lag in compensation, maternal blood pressure (BP) often falls slightly, by <5 mm Hg of systolic blood pressure (SBP), reaching a nadir ~20 to 22 weeks’ gestation before slowly rising back up to prepregnancy levels by term. After delivery, BP may transiently decrease before peaking after 5 to 7 days.

Despite these physiologic changes, hypertension is one of the most common medical problems encountered in pregnancy. Complicating 5% to 10% of all pregnancies, certain etiologies are associated with significant maternal and fetal morbidity and mortality, requiring prompt identification, intervention, and management.

ClassificationTop

Classification of hypertension in pregnancy:

1) Preexisting hypertension: Chronic hypertension diagnosed before pregnancy or hypertension occurring before 20 weeks’ gestation. It may also present as persistent hypertension >3 to 6 months into the postpartum period.

a) Essential hypertension: No secondary cause identified.

b) Secondary hypertension (hypertension with an identifiable cause): Consider endocrine, renal, cardiac, or vascular abnormalities, depending on the clinical presentation.

2) Gestational hypertension: Hypertension identified after 20 weeks’ gestation without other features of preeclampsia; it may evolve into preeclampsia.

3) Preeclampsia: Hypertension occurring after 20 weeks’ gestation with proteinuria, end-organ dysfunction, or both.

a) De novo preeclampsia: New-onset hypertension and proteinuria or end-organ dysfunction.

b) Preexisting hypertension with superimposed preeclampsia: Worsening hypertension with new or worsening proteinuria or end-organ dysfunction.

c) Preexisting proteinuria with superimposed preeclampsia: New or worsening hypertension with worsening proteinuria or end-organ dysfunction; this is often due to chronic kidney disease, and the diagnosis of superimposed preeclampsia is complex. Involvement of a specialist in renal disease in pregnancy is advisable.

DiagnosisTop

BP should be taken in a sitting rather than a supine position, as the gravid uterus may decrease venous return to the heart and produce abnormal increases or decreases in BP. Measurements should be taken with a manual sphygmomanometer. Ensure the cuff size is appropriate for the patient so as not to overestimate the measurement (such as can occur with a cuff size too small). Phase V (disappearance) rather than phase IV (muffling) of Korotkoff sounds should be used.

The diagnosis of hypertension in pregnancy is made when the patient has ≥2 readings >140/90 mm Hg, taken in the office or hospital, measured ≥15 minutes apart. The severity of hypertension is based on BP readings and evidence of end-organ damage. Nonsevere hypertension is considered any BP between 140 to 159 mm Hg SBP and 90 to 109 mm Hg diastolic BP (DBP). Severe hypertension is defined as a BP ≥160/110 mm Hg.

Isolated office (white coat) hypertension may be revealed by home blood-pressure measurement. If there is any conflict between home and office readings, a 24-hour ambulatory blood-pressure monitor can be considered.

All patients with hypertension diagnosed before or during pregnancy should be followed closely by an obstetrician. Baseline blood tests to look for causes of secondary hypertension and exclude end-organ involvement should be ordered at the first visit at which hypertension is diagnosed.

The issue of when to search for a possible cause of secondary hypertension (see Essential Hypertension) is not always clear. The need for other tests may be prompted by the clinical features or clinical course. At a minimum, electrolytes, creatinine (estimated glomerular filtration rate), and urinalysis should be ordered. It is our practice to also obtain a complete blood count and liver function tests to use as a baseline or, in the case of patients at >20 weeks’ gestation, to exclude end-organ involvement from preeclampsia. Further information may be taken into account when judging the need for additional investigations (Table 1).

Management and TreatmentTop

General Approach

Regardless of the etiology of hypertension (preeclampsia, preexisting, gestational), the pharmacologic treatment of hypertension in pregnancy is approached in a similar manner. However, unlike the management of nonpregnant patients, the decision to treat hypertension must consider the risks and benefits to both mother and fetus. For this reason, the initiation of antihypertensive therapy should always be undertaken in consultation with an obstetrician. It is also vital to determine the etiology of the hypertension (primary, secondary, pregnancy related) so that the clinical course and prognosis may be appropriately predicted.

1. General recommendations: BP levels, gestational age, and the presence of maternal and fetal comorbidities and complications must be taken into consideration.

1) Advise avoiding the supine position when lying down, as it may increase vasoconstriction.

2) Recommend maintaining a normal diet without salt restriction.

3) Normal physical activity need not be limited. Bed rest, unless in the setting of severely uncontrolled hypertension and/or severe preeclampsia, is not indicated.

2. Target BP and levels at which to start antihypertensive treatment are controversial. On the one hand, maternal risk of cerebral hemorrhage increases with BPs >160/110 mm Hg; on the other, aggressive lowering of BP may run the risk of compromising the uteroplacental blood supply due to reduced perfusion pressure into this largely passive vascular bed. Most clinicians will initiate treatment at levels >140 to 150 mm Hg SBP and >90 to 100 mm Hg DBP. A target DBP between 85 and 100 mm Hg in women with preexisting or pregnancy-induced hypertension (without preeclampsia) has historically been considered a safe zone for both mother and fetus. We suggest a target between 130 and 140 mm Hg SBP and 80 and 90 mm Hg DBP, recognizing that women with chronic hypertension who have BPs closer to 150/100 mm Hg run an increased risk of developing severe hypertension, preeclampsia, and adverse neonatal outcomes, and that slightly lower targets may also be reasonable.Evidence 1Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and indirectness. Magee LA, von Dadelszen P, Rey E, et al. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med. 2015 Jan 29;372(5):407-17. doi: 10.1056/NEJMoa1404595. PMID: 25629739. The CHIPS trial indicated that there is no difference in maternal or fetal outcome between patients for whom the target diastolic blood pressure was <100 mm Hg (less tight) versus those whose target was <85 mm Hg (tight) except for a greater frequency of severe hypertension (>160/110 mm Hg) in the former group. All patients in the CHIPS trial had either preexisting hypertension or essential hypertension at enrolment. Tita AT, Szychowski JM, Boggess K, et al; Chronic Hypertension and Pregnancy (CHAP) Trial Consortium. Treatment for Mild Chronic Hypertension during Pregnancy. N Engl J Med. 2022 May 12;386(19):1781-1792. doi: 10.1056/NEJMoa2201295. Epub 2022 Apr 2. PMID: 35363951; PMCID: PMC9575330. The CHAP trial enrolled pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of <23 weeks to receive antihypertensive medications recommended for use in pregnancy (active treatment group) or to receive no such treatment unless severe hypertension (SBP, ≥160 mm Hg; or DBP, ≥105 mm Hg) developed (control group). In pregnant women with mild chronic hypertension, a strategy of targeting a BP <140/90 mm Hg was associated with better pregnancy outcomes (preeclampisa, neonatal intensive care unit stay, preterm delivery) than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight.  

3. Treatment of nonsevere hypertension in pregnancy: First-line antihypertensive therapies include slow-release nifedipine, labetalol, or methyldopa (Table 2). These agents can be used alone or in combination as required. Second-line therapies (a fourth agent is rarely necessary) can include metoprolol, clonidine, hydralazine, or thiazide diuretics. Hydrochlorothiazide should be avoided if there is concern regarding a low amniotic fluid volume or in the setting of preeclampsia. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers are contraindicated.

4. Treatment of severe hypertension in pregnancy: Although there is still some divergence in opinion regarding the optimal BP cutoff at which to initiate medications and target treatment, a BP of 160 mm Hg SBP or 110 DBP should always be treated. In such cases, both maternal and fetal well-being must be assessed and hospital admission considered. Medications including IV labetalol, oral short-acting nifedipine, or IV hydralazine can be used. Our preference is to use short-acting nifedipine, as it has been found to be as effective and safe as IV labetalol and does not require a parenteral route.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision. Shekhar S, Sharma C, Thakur S, Verma S. Oral nifedipine or intravenous labetalol for hypertensive emergency in pregnancy: a randomized controlled trial. Obstet Gynecol. 2013 Nov;122(5):1057-63. doi: 10.1097/AOG.0b013e3182a9ea68. PMID: 24104790. Shekhar S, Gupta N, Kirubakaran R, Pareek P. Oral nifedipine versus intravenous labetalol for severe hypertension during pregnancy: a systematic review and meta-analysis. BJOG. 2016 Jan;123(1):40-7. doi: 10.1111/1471-0528.13463. Epub 2015 Jun 26. Review. PMID: 26113232. We prefer not to use hydralazine if other options are available. With all these drugs, small doses repeated every 30 to 40 minutes until the target BP is reached are the safest regimen; this allows the full effect of each incremental dose to be seen and avoids overdose and an inappropriate reduction in perfusion pressure (all 3 of these drugs have an onset within 20 min and a peak effect within 40 min, whether given orally or IV). Of note, responses of individual patients to different drugs may differ significantly. Medication doses: Table 3.

5. Postpartum management: After delivery, maternal BP often declines before rising once more between days 3 to 5 post partum, sometimes to levels higher than in pregnancy. Although this will often return to prepregnancy values within the following weeks, patients who have had a pregnancy complicated by hypertension may be particularly vulnerable to this postpartum surge, requiring an adjustment or addition of medication to prevent severe hypertension. All individuals with hypertension during pregnancy must be followed closely in the postpartum period. Nonsteroidal anti-inflammatory drugs for analgesia should be used judiciously, as they may aggravate hypertension. Any new or sudden worsening of hypertension with any associated signs and symptoms of end-organ dysfunction should prompt assessment for postpartum preeclampsia.

Antihypertensives used in pregnancy may be continued, as labetalol, slow-release nifedipine, and methyldopa are all considered safe in breastfeeding. However, ACEIs—particularly enalapril and quinapril—are both effective and safe and have the particular advantage that they have been shown not to cross into breast milk in an active form. Transition to prepregnancy medications may also be considered in the postpartum period. A target of <130/80 mm Hg, especially within the first 6 weeks postpartum, appears to be associated with improved BP readings at the 6-month and 3-year marks post partum, suggesting that adverse cardiac remodeling in women with hypertensive disorders of pregnancy may be exacerbated by poorly controlled BPs during the postpartum period, where normalization of cardiac changes in routine pregnancy occurs.Evidence 3Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to imprecision and indirectness. Kitt JA, Fox RL, Cairns AE, et al. Short-Term Postpartum Blood Pressure Self-Management and Long-Term Blood Pressure Control: A Randomized Controlled Trial. Hypertension. 2021 Aug;78(2):469-479. doi: 10.1161/HYPERTENSIONAHA.120.17101. Epub 2021 Jun 28. PMID: 34176288; PMCID: PMC8260340. Kitt J, Fox R, Frost A, et al. Long-Term Blood Pressure Control After Hypertensive Pregnancy Following Physician-Optimized Self-Management: The POP-HT Randomized Clinical Trial. JAMA. 2023 Nov 28;330(20):1991-1999. doi: 10.1001/jama.2023.21523. PMID: 37950919; PMCID: PMC10640702.

TablesTop